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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/30 09:06:32」(JST)

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Choroideremia ( /kɒˌrɔɪdɨˈriːmi.ə/) is an X-linked recessive retinal degenerative disease that leads to the degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye.

Choroideremia (CHM) is a rare inherited disorder that causes progressive loss of vision due to degeneration of the choroid and retina. It occurs almost exclusively in males. In childhood, night blindness is the most common first symptom. As the disease progresses, there is loss of vision, frequently starting as an irregular ring that gradually expands both in toward central vision and out toward the extreme periphery.

Progression of the disease continues throughout the individual's life. Both the rate of change and the degree of visual loss are variable among those affected, even within the same family.

The actual vision loss is caused by degeneration of several layers of cells that are essential to sight. These layers, which line the inside of the back of the eye, are called the choroid, the retinal pigment epithelium (RPE), and the retina. The choroid is a network of blood vessels located between the retina and the sclera, the "white of the eye." Choroidal vessels provide oxygen and nutrients to both the RPE and the retina's photoreceptor cells.

The RPE, directly beneath the retina, supports the function of photoreceptor cells. Photoreceptors convert light into the electrical impulses that transfer messages to the brain where "seeing" actually occurs. In the early stages of Choroideremia, the choroid and the retinal pigment epithelium initially deteriorate. Eventually, photoreceptor cells also degenerate. As a result, vision is lost.

Pathophysiology

Choroideremia is caused by the deletion of the Rab escort protein 1 (REP1). Rab escort protein 2 (REP2) is 75% identical and can almost compensate for the loss of REP1. Though the eye does express the REP2 protein (no cell could survive without some REP activity) evidently, in the eye, this is not enough. The REPs are essential for the prenylation of Rab proteins. Studies have shown that there is a build up of unprenylated Rab27 in lymphoblasts from Choroideremia patients. The link between the build up of unprenylated Rabs and blindness is not known.

Presentation

Generally, only men show symptoms of this disease, Initially a person suffering from choroideremia has night blindness, which begins in youth. As the disease progresses, a CHM sufferer loses their peripheral vision and depth perception, eventually losing all sight by middle age. In some cases, a severe loss of acuity and color perception become evident as the disease progresses.

The former UK Labour Member of Parliament Siôn Simon is a known sufferer.

The link between the loss of REP1 and the build up of unprenylated Rab27 and the degeneration of the eye is unknown as yet.

Prognosis

There is a genetic blood test to diagnose Choroideremia. It was created by Dr. Ian MacDonald at the University of Alberta. Free genetic testing is available for US and Canadian Residents through the eyeGENE project which is coordinated by the National Eye Institute at the US National Institutes of Health. Preclinical trial work is underway at the Imperial College of London under the direction of Dr. Miguel Seabra and at Moorfields Eye Hospital in London under the direction of Dr. Robert MacLaren. In the United States preclinical trial work is underway at the University of Pennsylvania under the direction of Dr. Jean Bennett and Dr. Albert Maguire. Dr. Ian MacDonald is also pursuing clinical trials at the University of Alberta in Canada. The Choroideremia Research Foundation, an international non-profit organization that for over ten years has been dedicated to raising awareness and securing funding for choroideremia research, is currently funding pre-clinical trial work for Dr. Seabra and Dr. Bennett. Dr. Ian MacDonald also serves on the board of directors for the CRF and receives funding from CRF-Canada. Human clinical trials could start as early as 2012. CRF-Canada also supports Dr. Seabra's and Dr. MacLaren's work as does Fight for Sight.

In a procedure first attempted at Moorfields Hospital in London, researchers at the John Radcliffe Hospital in Oxford have used gene therapy to attempt to curtail the condition which is caused by a faulty gene labelled REP1 and causes the light sensitive cells in the eye to gradually die. The procedure will halt the cell death by introducing functioning copies of the gene into the eye.^[1]

References

GeneReviews/NCBI/NIH/UW entry on Choroideremia

External links

Foundation Fighting Blindness
Choroideremia Research Foundation
Dr. Jean Bennett news on Leber Congenital Amaurosis Gene Therapy

References

^ Gene therapy used in a bid to save a man's sight

English Journal

A prenatally ascertained, maternally inherited 14.8Mb duplication of chromosomal bands Xq13.2-q21.31 associated with multiple congenital abnormalities in a male fetus.

Sismani C, Donoghue J, Alexandrou A, Karkaletsi M, Christopoulou S, Konstantinidou AE, Livanos P, Patsalis PC, Velissariou V.SourceDepartment of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Gene.Gene.2013 Nov 1;530(1):138-42. doi: 10.1016/j.gene.2013.08.032. Epub 2013 Aug 22.
Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq
PMID 23973723

Extraction of retinal tacks from subjects implanted with an epiretinal visual prosthesis.

de Juan E Jr, Spencer R, Barale PO, da Cruz L, Neysmith J.SourceDepartment of Ophthalmology, School of Medicine, University of California, San Francisco, CA, USA.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie.Graefes Arch Clin Exp Ophthalmol.2013 Oct;251(10):2471-6. doi: 10.1007/s00417-013-2452-y. Epub 2013 Sep 8.
BACKGROUND: Retinal tacks, first developed for the treatment of complex retinal detachments, have more recently been used for the fixation of epiretinal electrode arrays as part of implanted visual prostheses. Here, we report on the clinical experience of extracting four such tacks after chronic imp
PMID 24013578

Outer retinal tubulation in degenerative retinal disorders.

Goldberg NR, Greenberg JP, Laud K, Tsang S, Freund KB.Source*Vitreous, Retina, Macula Consultants of New York, New York, New York; †Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York; ‡Edward S. Harkness Eye Institute, Columbia University, New York, New York; and §Department of Ophthalmology, New York University School of Medicine, New York, New York.
Retina (Philadelphia, Pa.).Retina.2013 Oct;33(9):1871-6. doi: 10.1097/IAE.0b013e318296b12f.
PURPOSE: To demonstrate outer retinal tubulation (ORT) in various degenerative retinal disorders.METHODS: This was a retrospective review of the multimodal imaging of 29 eyes of 15 patients with various retinal dystrophies and inflammatory maculopathies manifesting ORT. The morphologic features of O
PMID 23676993

Japanese Journal

Clinical Findings in a Choroideremia Patient Who Underwent Vitrectomy for Retinal Detachment Associated with Macular Hole

SHINODA Hajime,KOTO Takashi,FUJIKI Keiko,MURAKAMI Akira,TSUBOTA Kazuo,OZAWA Yoko
Japanese journal of ophthalmology 55(2), 169-171, 2011-03-01
NAID 10029021013